PCYT2 encodes ethanolamine-phosphate cytidylyltransferase, which catalyzes the second step in phosphatidylethanolamine (PE) synthesis via the CDP-ethanolamine pathway. PE is a dominant inner-leaflet phospholipid that structurally stabilizes membrane-anchored proteins and participates in cell division, cell fusion, blood coagulation, and apoptosis. PCYT2 deficiency causes hereditary spastic paraplegia type 54 and developmental regression with global developmental delay. In muscle, PCYT2 activity is critical for cellular bioenergetics and membrane stability; human deficiency produces severe disease with failure to thrive and progressive weakness, while Pcyt2-mutant zebrafish and muscle-specific knockout mice recapitulate these phenotypes with accelerated ageing 1. PCYT2 activity declines in ageing muscles, and adeno-associated virus-mediated PCYT2 delivery ameliorates weakness in both Pcyt2-knockout and aged mice 1. In immune contexts, PCYT2 acts as a post-transcriptional regulator of T follicular helper cell differentiation by promoting surface expression of CXCR5, essential for humoral immunity 2. In colorectal cancer, PCYT2 suppresses metastasis by increasing YAP1 phosphorylation and subsequent degradation 3. Heterozygous Pcyt2 deletion causes age-dependent nonalcoholic steatohepatitis with metabolic dysregulation, reversible by supplementation with phosphoethanolamine 4. These findings position PCYT2 inhibition (via meclizine or nanoparticle delivery) as a therapeutic approach for liver regeneration in middle-aged mice 5.